Suppression of nonsense mutations as a therapeutic approach to treat genetic diseases

被引:74
作者
Keeling, Kim M. [1 ]
Bedwell, David M. [1 ]
机构
[1] Univ Alabama Birmingham, Dept Microbiol, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA
关键词
MESSENGER-RNA DECAY; TRANSLATIONAL TERMINATION EFFICIENCY; PREMATURE STOP MUTATIONS; CYSTIC-FIBROSIS PATIENTS; ALPHA-L-IDURONIDASE; DYSTROPHIN EXPRESSION; CRYSTAL-STRUCTURE; READ-THROUGH; IN-VITRO; AMINOGLYCOSIDE;
D O I
10.1002/wrna.95
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Suppression therapy is a treatment strategy for genetic diseases caused by nonsense mutations. This therapeutic approach utilizes pharmacological agents that suppress translation termination at in-frame premature termination codons (PTCs) to restore translation of a full-length, functional polypeptide. The efficiency of various classes of compounds to suppress PTCs in mammalian cells is discussed along with the current limitations of this therapy. We also elaborate on approaches to improve the efficiency of suppression that include methods to enhance the effectiveness of current suppression drugs and the design or discovery of new, more effective suppression agents. Finally, we discuss the role of nonsense-mediated mRNA decay (NMD) in limiting the effectiveness of suppression therapy, and describe tactics that may allow the efficiency of NMD to be modulated in order to enhance suppression therapy. (c) 2011 John Wiley & Sons, Ltd. WIREs RNA 2011 2 837-852 DOI: 10.1002/wrna.95
引用
收藏
页码:837 / 852
页数:16
相关论文
共 97 条
[11]  
Cassan M, 2001, BMC Mol Biol, V2, P3, DOI 10.1186/1471-2199-2-3
[12]   Comparison of cytotoxicity of aminoglycoside antibiotics using a panel cellular biotest system [J].
Chernikov, VG ;
Terekhov, SM ;
Krokhina, TB ;
Shishkin, SS ;
Smirnova, TD ;
Kalashnikova, EA ;
Adnoral, NV ;
Rebrov, LB ;
Denisov-Nikol'skii, YI ;
Bykov, VA .
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE, 2003, 135 (01) :103-105
[13]   No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations [J].
Clancy, John P. ;
Rowe, Steven M. ;
Bebok, Zsuzsa ;
Aitken, Moira L. ;
Gibson, Ron ;
Zeitlin, Pam ;
Berclaz, Pierre ;
Moss, Rick ;
Knowles, Michael R. ;
Oster, Robert A. ;
Mayer-Hamblett, Nicole ;
Ramsey, Bonnie .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2007, 37 (01) :57-66
[14]   Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis [J].
Clancy, JP ;
Bobök, Z ;
Ruiz, F ;
King, C ;
Jones, J ;
Walker, L ;
Greer, H ;
Hong, J ;
Wing, L ;
Macaluso, M ;
Lyrene, R ;
Sorscher, EJ ;
Bedwell, DM .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 163 (07) :1683-1692
[15]  
Clancy JP, 2006, PED PULMONOL S, V41, pA269
[16]   TransTerm, the translational signal database, extended to include full coding sequences and untranslated regions [J].
Dalphin, ME ;
Stockwell, PA ;
Tate, WP ;
Brown, CM .
NUCLEIC ACIDS RESEARCH, 1999, 27 (01) :293-294
[17]   New Therapeutic Approaches to Mendelian Disorders [J].
Dietz, Harry C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (09) :852-863
[18]   Nonsense Suppressor Therapies Rescue Peroxisome Lipid Metabolism and Assembly in Cells From Patients With Specific PEX Gene Mutations [J].
Dranchak, Patricia K. ;
Di Pietro, Erminia ;
Snowden, Ann ;
Oesch, Nathan ;
Braverman, Nancy E. ;
Steinberg, Steven J. ;
Hacia, Joseph G. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2011, 112 (05) :1250-1258
[19]   Nonaminoglycoside compounds induce readthrough of nonsense mutations [J].
Du, Liutao ;
Damoiseaux, Robert ;
Nahas, Shareef ;
Gao, Kun ;
Hu, Hailiang ;
Pollard, Julianne M. ;
Goldstine, Jimena ;
Jung, Michael E. ;
Henning, Susanne M. ;
Bertoni, Carmen ;
Gatti, Richard A. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (10) :2285-2297
[20]   PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model [J].
Du, Ming ;
Liu, Xiaoli ;
Welch, Ellen M. ;
Hirawat, Samit ;
Peltz, Stuart W. ;
Bedwell, David M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (06) :2064-2069